PHINDaccess Conference Omics Challenges in Infectious Diseases Research - Kick off meeting - November 5, 2018

1. Challenges and Opportunities for the Omics of Infectious Diseases
Jessica C Kissinger
University of Georgia, Department of Genetics, Institute of
Bioinformatics and Center for Tropical & Emerging Global Diseases,
Athens, GA
Dr. Jessica “Jessie" Kissinger is a distinguished professor of Genetics
and director of the Institute of Bioinformatics at the University of
Georgia. Her research focuses on the evolution of parasite genomes, in
particular, the genomes of organisms that cause malaria, toxoplasmosis
and cryptosporidiosis. Her research area has necessitated the
development of new computational tools to address issues of data integration and data mining in
addition to traditional wet laboratory experimentation. She built the computational infrastructure to
support the NIAID Malaria Host-Pathogen Interaction Center - MaHPIC and the DARPA Hammer
project focused on host resilience to malaria. She is a joint PI of the NIAID Bioinformatics Resource
Center, EuPathDB a family of databases which integrate large omic and population data sets for the
eukaryotic pathogen research community. It currently contains data for >300 organisms and has
average of ~70,000 accessions/month.
Abstract
We live in exciting times. The prospect to gain knowledge from data is immense yet the challenge of
collecting and integrating the data in order to gain knowledge is equally immense. I will discuss some
of the opportunities and challenges and finish with a tour of a database that comes close to meeting
many (but not all) infectious disease challenges. The Eukaryotic Pathogen Database (EuPathDB.org)
Bioinformatics Resource Center (BRC) provides online open access to genome sequences, omics
data and in some cases, associated microbiome, clinical and epidemiological data for >300 eukaryotic
pathogens of humans and animals including protists and fungi. EuPathDB is a collaboration between
researchers at the University of Pennsylvania, the University of Liverpool and the University of
Georgia.
EuPathDB integrates structured sample and clinical data from >500 datasets encompassing transcript
and protein expression, sequence and structural variation, epigenomics, clinical and field isolates,
metabolites and metabolic pathways and host-pathogen interactions. Data are analyzed using a
standardized workflow system ensuring that comparisons can be made across data sets. We have
learned much in our 15 years of accommodating data diversity, data quantity and community needs.
This resource is funded by NIH and augmented with funding from the Wellcome Trust and Bill &
Melinda Gates Foundation.
The C3BI, a multidisciplinary, transversal structure for large-scale data
processing
Angèle Bénard,
Trained originally as an engineer in biotechnology, I studied autoimmunity
and regulatory T cell development during my Ph.D.
I dedicated the following years to gain wide international research
experience. My interest grew toward the field of infectious diseases,
specifically ones of global health relevance, such as Buruli ulcer, a
neglected tropical disease, tuberculosis, chlamydia and cholera. Eventually,
during my last position at the Wellcome Trust Sanger Institute, I acquired
skills in bioinformatics and nurtured a keen interest for to its use and
applications in public health.
In parallel to my research, I recently completed an MBA in International Health Management, which
led me to join the Institut Pasteur as the Scientific and Administrative Deputy Director of the C3BI
earlier this year.

2. I believe that the use of big data and computational methods applied to biology will be a leverage point
in our fight to tackle the current global health inequities and the health challenges that the world
population will be facing in a near future such as emerging diseases and antibiotic resistance.
Christophe Malabat
After a PhD in biochemistry of the rapeseed proteins, during which I developed my
first automated scripts for handling data processing and analysis, I join Danone
research facility center for developing multivariate models for the prediction of milk
protein composition using infrared spectrometry.
As I was already developing my own informatics tools, I decided to join the course
of informatic for biology of the Institut Pasteur in 2007. At the end of the course I
was recruited by the Institute and integrate the unit of “génétique des interactions
macromoléculaires” of Alain Jacquier.
Within this group, I learn to handle sequencing data and I developed processing and analysis tools
using python and R.
I also create a genome browser and database system for storing, retrieving and visualizing microarray
data.
After 8 years within the Alain Jacquier’s lab, I join the Hub of bioinformatics and biostatistics as co-
head of the team.
Abstract
Thanks to the recent development and extensive use of high-throughput technologies, biological
laboratories are producing increasing volumes of -omics data in a high variety of formats.
Bioinformatics and computational biology hence become essential to process, analyse and decipher
the biological meaning of multi -omics data through mathematical modelling, statistics and computing.
The C3BI is a multi-disciplinary and transversal structure dedicated to the processing of large-scale
data at Institut Pasteur. Its mission is to strengthen bioinformatics and computational biology capacity
as well as facilitating interactions around these areas of research.
It develops methodological research in computer science and statistics, offers support to experimental
research units and works in conjunction with the Institut Pasteur International Network. The C3BI is
also responsible for developing bioinformatics activities and training in these fields within
the International Network. Antonio Borderia has been in charge of the portfolio and organisation of
these teaching & training international actions for more than 3 years now.
During my presentation, I will briefly introduce the organisation of the C3BI and the program of
International Actions of the C3BI. Furthermore, I will present a few examples of research
achievements undertaken at the C3BI in the field of infectious diseases and host-pathogen
interactions.
Open Science and Responsible Research and Innovation
Michela Bertero
Michela Bertero is the Head of International and Scientific Affairs at the Centre
for Genomic Regulation (CRG) in Barcelona (Spain). Her department´s mission
is to strengthen the international and interdisciplinary dimension of the institute
and create new opportunities for the scientific community by fostering new
strategic partnerships and alliances, coordinating international collaborative
projects, providing strategic advice and support to the Director and fostering
scientific talent through integrated training programmes. In the last few years,
she has been coordinating the scientific activities of the Severo Ochoa
programme of excellence. She played a fundamental role in the creation of the
European Alliance in life sciences, called EU-LIFE (www.eu-life.eu), that she is now representing in
the European Open Science Policy Platform advising Commissioner Moedas. She is also coordinating
the H2020 project ORION on Open Science.

3. Prior to joining the CRG, she worked as postdoctoral researcher in molecular and structural biology at
the Gene Center of the Ludwig Maximilian University in Munich (Germany), and at the University of
British Columbia in Vancouver (Canada), where she focused on the functional and structural
characterization of large macromolecular complexes, such the archeal RNA polymerase transcription
initiation complex and the membrane-bound respiratory complex Nitrate Oxido-Reductase A. Michela
holds a Ph.D. in Molecular Biology from the University of Pavia (Italy), where she studied transcription
regulation in bacterial motility.
Abstract
In 2011 the European Commission started promoting the concept of Responsible Research and
Innovation (shortly RRI) to “involve civil society very upstream” in the research process (Octavi
Quintana, Director of the European Research Area, EC 2011). In 2016 the European Commissioner
for Research, Science and Innovation, Carlos Moedas, published the book on “Open Innovation, Open
Science, Open to the World” bringing forward the concept of Open Science as “new approach to the
scientific process based on cooperative work and new ways of diffusing knowledge by using digital
technologies and new collaborative tools”. RRI and Open science are now promoted in parallel at
European level (and beyond), sharing several objectives – including open access to scholarly
publications, open data, stakeholder engagement, ethics and research integrity. The European
Commission has already funded multiple projects in RRI and Open Science to develop policy
frameworks, training and practical examples of implementation. I will introduce an H2020 specific
project, called ORION, aiming at practising Open Science and RRI in life sciences and present
preliminary results to explore potential synergies with PHINDaccess.
H3ABioNet: Informatics solutions for Africa
Alia Benkahla
Dr Alia Benkahla is a bioinformaticist she did her PhD studies at the IGS-CNRS in Marseille. Her initial
training was in Mathematics. She worked as Post-Doctoral fellow at the Max-Planck Institute in Berlin,
and moved to the Institut Pasteur de Tunis in January 2005. She initiated the Group of Bioinformatics
and Mathematical Modeling and invested her initial period at IPT in capacity building in the field of
Bioinformatics by: training students; co-organizing international events in Africa; networking in the field
de Bioinformatics; and looking for funds in Bioinformatics for Tunisia’s and Africa’s health issues. She
is the President of the African Society of Bioinformatics and Computational Biology since September
2015. She was the chair of the third ISCB Africa ASBCB Conference on Bioinformatics 2013. She is
head of the Laboratory BioInformatics, bioMathematics and biostatistics (BIMS). She was the PI of 6
research projects and is the PI of the actual H3ABioNet Tunisian node. She is member of the
Scientific and Training Advisory Board of the Wellcome Trust DELTAS project: “Developing
Excellence in Leadership and Genetic Training for Malaria Elimination in Sub-Saharan Africa
(DELGEME)” and is member of the Technical Advisory Committee of the “NIH Global Health
Bioinformatics Research Training for West-Africa - WASLITBRe” and of the “West African Center of
Excellence for Global Health Bioinformatics Research Training”. She is co-coordinating the H3Africa
Phenotype Harmonization WG. Her research is mainly in the area of systems biology aimed at
understanding processes of regulation, interaction, signaling mechanisms activated in response to
diseases (i.e., leishmaniasis and/or tuberculosis, cancer).
She is co-author of 25 publications among which: 3 Nature, 2 Sciences and co-author of 2 book
chapters.
Alan Christoffels is the Director of the South African National Bioinformatics
Institute and the DST/NRF Research in Bioinformatics and Public Health
Genomics. After completing his studies in 2001, he moved to Singapore for a
postdoc in the Sydney Brenner lab with a focus on genome evolution. During
this time he contributed to the annotation and genome analysis of the

4. Pufferfish genome and developed method for detecting genome duplication events. This methodology
was later used in other international genome projects while he established his group in Singapore in
2004. In 2007 he returned to South Africa and established his group at the South African National
Bioinformatics Institute based on the University of the Western Cape campus. He has driven a number
genomics projects on the African continent. During the past 4 years his team has focused on
infectious disease models including M.tuberculosis. The Christoffels laboratory has been building
tools and analyzing data that leads to a better understanding of host-pathogen interactions. Central to
these methods is a computational platform that relies on reproducible workflows and a graph
database. The ultimate goal is to ensure that these methods are readily accessible by biomedical
researchers with a view of improved disease surveillance.
Abstract
Development of a computational platform for tuberculosis research
COMBAT-TB: Computational Bacterial Analytical Toolkit for Tuberculosis Research
Despite the substantial information and communication technology (ICT) investment in Africa, recent
reports suggest that Africa is losing ground with regard to a digital knowledge economy as measured
by number of academic papers, innovative technologies and skills development. These findings
remind us that Africa’s ICT investment cannot only be driven by faster internet access. In the context
of disease surveillance, a pan African coordinated effort is required to ensure rapid access to real-time
data that can inform a public health response to a disease outbreak.
Responding to emerging pathogen threats require robust scalable integrated platforms that can handle
a range of data-types. An integrated platform for disease surveillance in Africa requires innovative
technologies that can:
(1) Store meta-data - information including clinical, genomics and demographical,
(2) Enable data provenance tracking – capturing what happens to data throughout its life cycle,
(3) Facilitate rapid on-site data analyses i.e., migrate analytics to, and not data from, the research
sites,
(4) Share information in real-time to stakeholders
The above criteria informed the development of the COMBAT-TB platform. The presentation will focus
on graph storage, workflows and data integration to deliver on the analysis of pathogen data.
Revisiting the evolutionary history of Yersinia pestis: zooming into the
second plague pandemic with new ancient genomes
Amine Namouchi
Since my PhD (2008) at the Institut Pasteur in Tunis (Tunisia), I was actively
involved in several international projects that converged to one central question:
why some bacterial pathogenic clones are more successful than others in terms
of virulence and transmission.
After my PhD, I spent more than five years at the Institut Pasteur in Paris
(France) where I was involved in several projects related to the driven forces
that govern the Mycobacterium tuberculosis genome evolution. I was also
involved in drug discovery projects with the aim to understand the mode of action of new compounds
and pathways to treat Tuberculosis.
After my experience at the Pasteur Institute, I moved to Norway to worked at the Centre for Ecological
and Evolutionary Synthesis at the University of Oslo. I am in charge of tracing back the evolutionary
history of Yersinia pestis, the causative agent of plague, during the Medieval period in Europe by
combining metagenomics and phylogenomics using modern and ancient DNA.
Abstract

5. The Second Plague Pandemic started in the mid 14
th
century and lasted until the 19
th
century. Its
beginning in Europe is marked by a major epidemic event commonly referred to as the Black Death
(1346 - 1353), which ultimately led to the death of at least 30% of the European population.
Over the last few years, genomic studies on Yersinia pestis, the causative agent of all known plague
epidemics, have considerably increased in numbers. I will share with you the results of our
comprehensive revision of the current phylogeny of Y. pestis strains from recent isolates back to
Bronze Age samples, spanning a period of about 5,000 years. Moreover, I will describe several new
identified ancient genomes dated to the Medieval period. These newly described genomes
significantly increase the resolution of the previous phylogeny of Y. pestis. We evaluated our results in
light of published historical, epidemiological and ecological studies in order to improve our
understanding of disease dynamics during the Second Plague Pandemic.
Computational Challenges in Metagenomic Pathogen Identification
Bernard Renard
Dr. Bernhard Renard heads the Bioinformatics Division at Robert Koch Institute
(RKI) in Berlin/Germany. He further serves as deputy head of the department
for methods development and research infrastructure at RKI and is Professor at
the Department of Mathematics and Computer Science at Freie University
Berlin and Associated Faculty at the International Max Planck Research School
for Computational Biology. A biostatistician as well as information engineer by
training, Bernhard holds a PhD in interdisciplinary informatics from the
University of Heidelberg. His research interests are in pathogen bioinformatics
and the analysis of omics data, in particular from metagenomics and metaproteomics experiments as
well as in the development of corresponding bioinformatics software
(https://gitlab.com/rki_bioinformatics/).
Abstract
Next-generation sequencing has become a workhorse for in time-critical applications such as disease
outbreak analysis and there is a strong need for fast turnaround time. While runtime of data analysis
software has significantly decreased and more powerful computational resources became available,
the overall turnaround time from sample arrival to analysis results remained nearly the same due to
the sequential paradigm of data production and analysis. We developed and have routinely applied a
collection of tools for sequence analysis while the sequencer is still running even for high throughput
Illumina runs. In doing so, intermediary results can be obtained for four crucial steps in time-critical
workflows: read alignment, read filtering, metagenomic classification and diagnostics. While giving first
insights into the data in early stages of sequencing, final results are provided only a few minutes after
sequencing finished. We further explore challenges arising from exponentially growing reference
database sizes, but also from their inherent incompleteness.